Metered-dose inhalers (MDIs) are medication delivery devices that deliver a pharmaceutical formulation including one or more pharmaceutically active compounds (“active ingredients”) to a human or other mammalian patient.
Typically the pharmaceutical formulation is delivered by the MDI as unit doses in the form of an aerosol. Each actuation of the MDI delivers one unit dose. The unit dose is expelled by the MDI and is taken into the body of the patient on inhalation, via the nose or mouth. The pharmaceutical formulation is delivered to or via the respiratory tract, notably to the lungs, of the patient on inhalation.
The MDI includes a metering valve which is configured to ensure that each dose of the pharmaceutical formulation expelled by the MDI is the same, within permitted tolerances. In particular, each dose should include the same amount of the active ingredient(s). Generally, the metering valve is configured to dispense a constant volume of the pharmaceutical formulation on each actuation of the MDI.
Metered-dose inhalers are typically used for the treatment of respiratory infections and disorders including respiratory tract infections, obstructive lung disease, inflammatory lung disease and chronic obstructive pulmonary disease. Asthma treatment is a particularly common use of MDIs.
MDIs may be used to deliver various types of active ingredients as appropriate to the medical condition of the patient being treated including, by way of example, bronchodilators (β2 agonists and anticholinergics) and corticosteroids.
A metered-dose inhaler typically includes a canister made from aluminum or steel and an actuator. The canister houses a pharmaceutical (therapeutic) formulation, which generally includes one or more active ingredients and a liquefied gas propellant. The formulation may also include various other components, such as stabilizing excipients.
The canister includes the metering valve at one end. The metering valve is typically contained within a neck portion of the canister and includes a valve stem extending outwardly from the canister through which valve stem the pharmaceutical formulation is dispensed.
The canister may be positioned in an actuator, which may typically include an approximately cylindrical body portion into which the canister is received and a discharge nozzle or sleeve, often called a “valve stem block,” which communicates with a discharge opening. The discharge opening may be a mouthpiece opening or nosepiece opening, as appropriate to the delivery mode and is configured accordingly. When the canister is fully received in the actuator body portion to achieve its operational configuration, a portion of the length of the valve stem of the metering valve is received in the actuator discharge sleeve. The actuator discharge sleeve typically includes a shoulder or ledge against which a forward-most end of the valve stem rests when the canister is fully received into the actuator body portion.
For actuation of the MDI to dispense the unit dose, the user presses the base of the canister to urge the canister forwardly into the actuator. The shoulder or ledge of the discharge sleeve prevents forward movement of the valve stem relative to the actuator. The valve stem is thus moved along a line of action relative to the container. In other words, the valve stem is depressed partially into the container. This depression of the valve stem results in the discharge of the unit dose of the pharmaceutical formulation through the valve stem and the stem block and consequently through the discharge opening for delivery to the patient. On release of the canister by the user, the valve stem is biased to return to its initial position.
A metered-dose inhaler contains enough of the pharmaceutical formulation in the canister for a certain number of actuations, equating to a certain number of unit doses. The number of doses is determined by the supplier of the MDI to ensure that for each actuation of the MDI within that number of doses, the patient consistently receives the same unit dose of the pharmaceutical active. However, the inhaler may continue to operate after the determined number of actuations has been reached. This carries the significant risk that for such “excess” actuations, the amount of pharmaceutical active being delivered to the patient may not be correct and in particular may be insufficient. It may be very difficult for a patient accurately to count the number of actuations (and thus the number of doses) used or delivered in order to ensure that the determined number of doses is not exceeded.
Although efforts have been made to provide mechanical dose counters, these dose counters may add significant cost and materials to the device and may be inaccurate. Mechanical dose counters may not be able to differentiate events when a dose is actually delivered as compared with other events, such as when a metered-dose inhaler is dropped on the ground or otherwise experiences movement that does not press the metering valve sufficiently for a dose to be delivered. Hence mechanical dose counters have not gained widespread acceptance from healthcare providers.
Electro-mechanical and electronic dose counters have also been proposed but have yet to achieve a sufficiently low cost and sufficiently high reliability. In particular, the problem of false counts (such us when the MDI is accidentally dropped) has not been resolved and difficulties persist and providing a power source which is suitably compact and cheap and which can reliably provide power throughout the full service life of the MDI.
US 2010/0078447 to Sauzade et el proposes a detection arrangement for detecting the dispensing of a fluid from a metering valve, such as of an inhaler for nasal use. The detector detects the passage of the fluid between the metering valve and a dispensing orifice and provides a “signal” intended to inform the user that a dose had been dispensed. In embodiments, the detector comprises a piezoelectric material, such as PVDF, in the form of a membrane which surrounds the channel through which the fluid is dispensed. Pressure changes in the channel as fluid is dispensed cause a deformation of the membrane thereby generating the dispensing signal.
US 2011/0041845 to Solomon describes an MDI with a dose counter which relies on a force sensor located on the base of the canister. Actuation of the MDI by depression of the canister thus generates a force signal which is used to advance the dose counter. The requirement to place the force sensor on the base of the canister is disadvantageous, not least in terms of patient acceptance and compliance. The force sensor of US 2001/0041845 is also used to capture data relating to the pressure gradient and duration of each activation. An algorithm is used which advances the dose counter only when the detected pressure profile of the activation closely matches a previously determined profile known to be required in order to “fire” the canister and deliver a dose.